The present invention provides isolated human and bovine TNF-.alpha. convertases, nucleic acids and; recombinant vectors encoding the same, host cells comprising the nucleic acids and vectors, and methods for making the convertases using the host cells. This invention further provides antibodies and antigen binding fragments thereof which specifically bind to the convertases and are useful for treating medical conditions caused or mediated by TNF-.alpha.. Also provided are screening methods for identifying specific inhibitors of mammalian TNF-.alpha. convertases, and for identifying nucleic acids encoding such convertases.